title: Brain acetylcholinesterase promotes amyloid-beta-peptide aggregation but does not hydrolyze amyloid precursor protein peptides.
abstract: It has been suggested that acetylcholinesterase (AChE) has both a putative proteolytic activity against the amyloid precursor protein (APP), and a capacity to accelerate the assembly of amyloid-beta-peptide (Abeta) into Alzheimer's fibrils. Here, we have studied the ability of bovine brain AChE to share both activities. Results indicate that AChE purified through acridinium was able to process the APP peptides, however after further purification by an edrophonium column, the protease activity was lost. Under both conditions the capacity of the enzyme to promote amyloid formation was maintained. Kinetic studies of the Abeta aggregation process using edrophonium-AChE, indicated that the lag phase of the aggregation process was smaller than the one observed with the esterase purified by acridinium alone. Considering that the total amount of amyloid formed, measured by thioflavine-T fluorescence, was similar for both AChE preparations, our results suggest that the edrophonium-AChE possesses an higher intrinsic capacity to stimulate the aggregation of Abeta(1-40) peptide.
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago-Chile.
authors.forename: E O
authors.initials: EO
authors.lastname: Campos
authors.forename: A
authors.initials: A
authors.lastname: Alvarez
authors.forename: N C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D000110:Acetylcholinesterase